The present application relates to methods and compositions for remineralization of the teeth due to mineral loss related dental conditions such as dental caries and/or dental erosion.
Dental caries (tooth decay) is a prevalent chronic disease affecting 60% to 90% of school-aged children in industrialized countries and the vast majority of adults. It is a significant cause of hospital admissions, emergency department care and the use of general anesthetics among young children. In the United States, dental caries is the single, most common chronic disease of childhood. Its prevalence (59%) among children is 5 times more common than asthma (11%) and 7 times more common than hay fever (8%). (US Department of Health and Human Services. Oral Health in America: A Report of the Surgeon General. (2000)). The National Health and Nutrition Examination Survey (NHANES) 1999-2004 data showed that 28% of 2-5 year olds in the U.S. have caries in their primary teeth and the prevalence increased by 15% during the last decade. (CDC Morbidity and Mortality Weekly Report 54, 1-44 (2005), Dye, B. A. et al. Trends in oral health status: United States, 1988-1994 and 1999-2004. Vital Health Stat 11, 1-92 (2007)). The treatment of dental caries is expensive, representing roughly 60% of annual dental health care costs and averaging 6% of total and 16% of private healthcare expenditure in developed countries. (Organization for Economic Co-operation and Development (OECD). Health at a Glance, 2009: OECD Indicators. (2009).)
Childhood dental caries often goes untreated; thereby exacerbating the problem and leading to many serious co-morbidities, including chronic pain, tooth loss, difficulty hearing, eating, speaking, sleeping, and failure to thrive, as well as poor school performance, social relationships, and self-image, and decreased success later in life. Because of disease burden, co-morbidities, and negative social consequences, dental caries has become a focal issue in efforts to reduce public health disparities for both NIDCR and the American Academy of Pediatrics. Over the past 40 years, fluoride has been the cornerstone for caries prevention. Also during that time, the number of different sources of fluoride has increased and now includes a variety of sources, such as fluoride dentifrices, fluoride gel, and other therapeutic fluoride products. Even with such a high availability, the caries-preventive effect of fluoride use has been leveled off and the prevalence of mild dental fluorosis has significantly increased during the last several decades. Fluoride toothpaste is most widely used fluoride modality, but conventional fluoride toothpaste has a significant caries-preventive effect only at concentrations of 1,000 parts per million (ppm) or higher. However this concentration of toothpaste is associated with an increased risk of fluorosis when used by young children under the age of 6, particularly before two years old. The first two years of life has been identified as most important to fluorosis development for early-erupting permanent teeth, such as incisors and first molars. (Hong, L., Levy, S. M., Warren, J. J., Broffitt, B. & Cavanaugh, J. Fluoride intake levels in relation to fluorosis development in permanent maxillary central incisors and first molars. Caries Res 40, 494-500 (2006). Hong, L. et al. Timing of fluoride intake in relation to development of fluorosis on maxillary central incisors. Community Dent Oral Epidemiol 34, 299-309 (2006).) Thus, the anti-caries effect of traditional fluoride therapy has a limitation.
Non-fluoride topical remineralizing agents containing calcium and/or phosphate has been investigated and showed the potential as an alternative to fluoride or as an adjunct to fluoride to enhance its effectiveness at lower fluoride concentration. Such agents would be of particular benefit to children to reduce the risk of fluorosis as well as to prevent caries. Casein Phosphoprotein-amorphous calcium phosphate (CPP-ACP) is currently most commonly used in clinic. Although there is substantial laboratory and in situ evidence for a benefit, recent review of current clinical trial data by the American Dental Association (ADA) Council on Scientific Affairs (CSA) reported that the evidence is weak and insufficient to support recommending any of the current mineral formulations for caries reduction, including CPP-ACP based products (Rethman, M. P. et al. Nonfluoride caries-preventive agents: executive summary of evidence-based clinical recommendations. J Am Dent Assoc 142, 1065-1071 (2011)). Calcium-Phosphate (Ca—P) compounds have been added to a variety of topical delivery vehicles and are commercially available in toothpaste, chewing gum, varnish, and mouth rinse. (Zero, D. T. Dentifrices, mouthwashes, and remineralization/caries arrestment strategies. BMC Oral Health 6 Suppl 1, S9 (2006)). The significant problem with CPP-ACP is its low solubility in acidic microenvironment where tooth demineralization occurs. The problem of stabilizing calcium and phosphate ions so that bioavailable Ca—P can be delivered when needed is a major challenge which impedes a large scale, population-based utilization of Ca—P-based products for caries prevention and control. Thus CPP-ACP products cannot deliver fresh ACP quickly at an adequate level for remineralization when the tooth is attacked by the acids produced by oral bacteria. There is a continued need to search for a better delivery system of calcium and phosphate to the teeth.
Accordingly, there is a need for compositions and methods to prevent and treat dental erosion and/or dental caries in patients exhibiting dental erosion and/or dental caries, especially in children. Additional and more effective compositions and methods are needed to remineralize the teeth. Patients suffering from dental erosion and or dental caries are in urgent need of alternatives to fluoride therapy.